Nanotechnology approaches for global infectious diseases

In the paper

“The results demonstrated that while free imipenem had negligible effect when co-administered with the enzyme, the nanoparticles had comparable bactericidal effects regardless of whether carbapenemase had been co-administered.”

What the sources say

• Partly supported

  In Results and discussion, ‘Protection from carbapenemases’ (page not provided), the paper says free imipenem lost all activity after enzyme treatment, while both nanoparticle formulations retained inhibitory effects. It does not establish that the nanoparticles killed bacteria or that their effects were comparable in magnitude with and without enzyme treatment; the assay measured growth-inhibition zones. (LLM, conf=0.84)

  cites [82] Shaaban, M. I., Shaker, M. A. & Mady, F. M. Imipenem/cilastatin encapsulated polymeric nanoparticles for destroying carbapenem-resistant bacterial isolates. J. Nanobiotechnol. 15, 29 (2017). sourceExperimental — accuracy not yet measured

In the paper

“Mortality rates are highest in developing countries, where resources such as vaccines and anti-infectives may be limited (Fig. 1b) 1 .”

What the sources say

• Not checked yetcites [1] Roth, G. A. et al. Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980–2017: a systematic analysis for the global burden of disease Study 2017. Lancet 392, 1736–1788 (2018). source

In the paper

“Temporal trends in mortality show that although the overall number of deaths is declining, the gap between deaths in high socio-demographic index (SDI) countries and low SDI countries remains substantial (Fig. 1c) 1 .”

What the sources say

• Not checked yetcites [1] Roth, G. A. et al. Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980–2017: a systematic analysis for the global burden of disease Study 2017. Lancet 392, 1736–1788 (2018). source

In the paper

“In some cases, a lack of drug efficacy can be attributed to pathogen resistance, which then requires a more expensive drug regimen for cure 3 .”

What the sources say

• Not checked yetcites [3] Munita, J. M. & Arias, C. A. Mechanisms of antibiotic resistance. Microbiol. Spectrum 4, VMBF-0016-2015. (2016). source

In the paper

“Nanotechnology has the potential to transform both detection and treatment of a wide range of diseases.”

In the paper

“Poor patient adherence to therapies and the need for sustained patient monitoring are major obstacles to effective treatment 4 .”

What the sources say

• Not checked yetcites [4] Sabaté, E. Adherence to Long-Term Therapy: Evidence for Action (WHO, 2003).

In the paper

“High mortality rates are associated with lower respiratory infections, diarrhoea, tuberculosis (TB), human immunodeficiency virus (HIV) infection and malaria (Fig. 1a) 1 .”

What the sources say

• Not checked yetcites [1] Roth, G. A. et al. Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980–2017: a systematic analysis for the global burden of disease Study 2017. Lancet 392, 1736–1788 (2018). source

In the paper

“Infectious diseases are a major driver of morbidity and mortality globally.”

What the sources say

• Not checked yetcites [1] Roth, G. A. et al. Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980–2017: a systematic analysis for the global burden of disease Study 2017. Lancet 392, 1736–1788 (2018). source

In the paper

“Poor procurement practices, the inability to pay for drugs and poor stability of drug products at high temperature and humidity prevent access to effective treatments 5 .”

What the sources say

• Not checked yetcites [5] Pheage, T. Dying from Lack of Medicines (United Nations, 2016); https://www.un.org/africarenewal/magazine/december-2016-march-2017/dying-lack-medicines source

In the paper

“Nanosystems have been the subject of intensive research over the past few decades, resulting in Food and Drug Administration (FDA)-approved chemotherapeutics, anaesthetics, imaging agents, nutritional supplements and others 6 .”

What the sources say

• Not checked yetcites [6] Anselmo, A. C. & Mitragotri, S. Nanoparticles in the clinic. Bioeng. Transl. Med. 1, 10–29 (2016). source

In the paper

“The highest tissue uptake was achieved with PEG-coated nanoparticles; however, tissue uptake was limited to the lower reproductive tract.”

What the sources say

• Not checked yetcites [23] Cu, Y., Booth, C. J. & Saltzman, W. M. In vivo distribution of surface-modified PLGA nanoparticles following intravaginal delivery. J. Control. Release 156, 258–264 (2011). source

In the paper

“A drawback of some polymeric and liposomal formulations is that they require large quantities of excipients to control drug release. This increases the size of the injection and limits the amount of drug that can be administered.”

In the paper

“Cunha-Reis et al. demonstrated that nanoparticles loaded with an anti-HIV drug (efavirenz) and embedded in a water-soluble film showed lower leakage and enabled higher tissue concentrations than nanoparticle dispersions 25 .”

What the sources say

• Not checked yetcites [25] Cunha-Reis, C. et al. Nanoparticles-in-film for the combined vaginal delivery of anti-HIV microbicide drugs. J. Control. Release 243, 43–53 (2016). source

In the paper

“In a rat model, intravenously administered Mikasomes distributed to several tissues, where they released drug gradually resulting in an eightfold increase in drug half-life.”

What the sources say

• Not checked yetcites [14] Fielding, R. M., Lewis, R. O. & Moon-McDermott, L. Altered tissue distribution and elimination of amikacin encapsulated in unilamellar, low-clearance liposomes (MiKasome). Pharm. Res. 15, 1775–1781 (1998). source

In the paper

“Acyclovir monophosphate nanoparticles protected ~54% of the mice that were infected with HSV-2 30 min post-treatment. In contrast, the soluble drug protected only 16% of the mice from viral challenge.”

What the sources say

• Not checked yetcites [26] Ensign, L. M. et al. Mucus-penetrating nanoparticles for vaginal drug delivery protect against herpes simplex virus. Sci. Transl. Med. 4, 138ra79 (2012). source

In the paper

“Nanocarriers can be engineered to release drugs in the presence of certain triggers and provide temporal control on drug exposure.”

In the paper

“Encapsulation of drugs in nanocarriers allows for sustained drug delivery, thereby reducing dosing frequency.”

In the paper

“Drug release occurs via bulk degradation of the polymer and drug diffusion 12 and can be modified by altering the hydrophobicity of the monomer, polymer chain length and particle size 13 .”

What the sources say

• Not checked yetcites [12] Langer, R. Drug delivery and targeting. Nature 392, 5–10 (1998).
• Not checked yetcites [13] Makadia, H. K. & Siegel, S. J. Poly lactic-co-glycolic acid (PLGA) as biodegradable controlled drug delivery carrier. Polymers 3, 1377–1397 (2011). source

In the paper

“Nanocarriers may enhance drug uptake in cells and improve efficacy against intracellular pathogens.”

In the paper

“An important consideration with sustained release systems is the potential for prolonged exposure to sub-therapeutic concentrations, which may lead to drug resistance 19 .”

What the sources say

• Not checked yetcites [19] Wistrand-Yuen, E. et al. Evolution of high-level resistance during low-level antibiotic exposure. Nat. Commun. 9, 1599 (2018). source

In the paper

“Compared with healthy mice, the transfection efficiency of the polyplex in mice treated with lipopolysaccharide was reduced by about tenfold. Impressively, pre-treatment with N -acetyl cysteine restored transfection efficiency in the inflammation model.”

What the sources say

• Not checked yetcites [36] Suk, J. S. et al. N-acetylcysteine enhances cystic fibrosis sputum penetration and airway gene transfer by highly compacted DNA nanoparticles. Mol. Ther. 19, 1981–1989 (2011). source

In the paper

“The scaffold did enable the slow release of silver; however, toxicity to host cells was not reduced 40 .”

What the sources say

• Not checked yetcites [40] Mohiti-Asli, M., Pourdeyhimi, B. & Loboa, E. G. Skin tissue engineering for the infected wound site: biodegradable PLA nanofibers and a novel approach for silver ion release evaluated in a 3D coculture system of keratinocytes and Staphylococcus aureus. Tissue Eng. Pt C 20, 790–797 (2014). source

In the paper

“These results suggest that the presence of biofilms plays a role in chronic infections and non-healing wounds, and strategies that overcome biofilm resistance may help treat these infections.”

In the paper

“Interestingly, PLGA nanoparticles containing cationic spermidine have been used for siRNA-based knockdown of the same target, and have shown better protection than lipofectamine lipoplexes 28 .”

What the sources say

• Not checked yetcites [28] Steinbach, J. M., Weller, C. E., Booth, C. J. & Saltzman, W. M. Polymer nanoparticles encapsulating siRNA for treatment of HSV-2 genital infection. J. Control. Release 162, 102–110 (2012). source

In the paper

“The authors found that the PLGA nanoparticles had a similar knockdown efficiency to lipoplexes, but elicited lower inflammation (as observed by measuring neutrophil invasion using immunohistochemistry).”

What the sources say

• Not checked yetcites [28] Steinbach, J. M., Weller, C. E., Booth, C. J. & Saltzman, W. M. Polymer nanoparticles encapsulating siRNA for treatment of HSV-2 genital infection. J. Control. Release 162, 102–110 (2012). source

In the paper

“aminoglycosides largely accumulate in the lysosomes and are likely to be ineffective against cytosolic pathogens 64 .”

What the sources say

• Not checked yetcites [64] Tulkens, P. & Trouet, A. The uptake and intracellular accumulation of aminoglycoside antibiotics in lysosomes of cultured rat fibroblasts. Biochem. Pharmacol. 27, 415–424 (1978). source

In the paper

“In rats, 60% of the drug dose was found in the RES organs 8 h after treatment with nanoparticles. In contrast, after treatment with the soluble drug alone, only 12% of the drug was recovered in the RES tissues.”

What the sources say

• Not checked yetcites [44] Löbenberg, R., Araujo, L., von Briesen, H., Rodgers, E. & Kreuter, J. Body distribution of azidothymidine bound to hexyl-cyanoacrylate nanoparticles after i.v. injection to rats. J. Control. Release 50, 21–30 (1998). source

In the paper

“Encapsulation in nanocarriers offers opportunities to increase cell uptake of anti-infectives and alter their intracellular disposition (Fig. 4b).”

In the paper

“Nanoparticle-based treatment enabled a tenfold dose reduction in vivo.”

What the sources say

• Not checked yetcites [55] Arias, J. L. et al. Nanobody conjugated PLGA nanoparticles for active targeting of African trypanosomiasis. J. Control. Release 197, 190–198 (2015). source

In the paper

“Resistance results from the secretion of drug-inactivating enzymes and/or the pathogens switching to a state of reduced metabolic activity, forming biofilms, adopting an intracellular life cycle or being obligate intracellular pathogens 3 .”

What the sources say

• Not checked yetcites [3] Munita, J. M. & Arias, C. A. Mechanisms of antibiotic resistance. Microbiol. Spectrum 4, VMBF-0016-2015. (2016). source

In the paper

“InvA497-funtionalized gentamycin-loaded liposomes caused a 30% reduction in bacterial load in an in vitro model of Y. pseudotuberculosis infection, whereas albumin-functionalized liposomes had no effect 68 .”

What the sources say

• Not checked yetcites [68] Labouta, H. I. et al. Bacteriomimetic invasin-functionalized nanocarriers for intracellular delivery. J. Control. Release 220, 414–424 (2015). source

In the paper

“Animals treated with mRNA nanoparticles produced antibody-based and CD8 + T-cell immune responses, and were completely protected from lethal challenges of Ebola virus, H1N1 influenza and Toxoplasma gondii .”

What the sources say

• Not checked yetcites [75] Chahal, J. S. et al. Dendrimer-RNA nanoparticles generate protective immunity against lethal Ebola, H1N1 influenza, and Toxoplasma gondii challenges with a single dose. Proc. Natl Acad. Sci. USA 113, E4133–E4142 (2016). source

In the paper

“Nanoparticles formed from this conjugate were rapidly taken up by cells and released drug in the endolysosomes. This resulted in improved activity over the free drug.”

What the sources say

• Not checked yetcites [67] Sémiramoth, N. et al. Self-assembled squalenoylated penicillin bioconjugates: an original approach for the treatment of intracellular infections. ACS Nano 6, 3820–3831 (2012). source

In the paper

“A key feature of nanocarriers is that they aid in the transport of mRNA across the cell membrane, enable endolysosomal escape and release the nucleic acid in the cytoplasm 74 .”

What the sources say

• Not checked yetcites [74] Kowalski, P. S., Rudra, A., Miao, L. & Anderson, D. G. Delivering the messenger: advances in technologies for therapeutic mRNA Delivery. Mol. Ther. 27, 710–728 (2019). source

In the paper

“Initial results with lipid-nanoparticle-formulated mRNA vaccines against H10N8 and H7N9 influenza viruses and SARS-CoV-2 indicate that these vaccines are well tolerated and that they produce a robust humoral response 76,77 .”

What the sources say

• Not checked yetcites [76] Jackson, L. A. et al. An mRNA vccine against SARS-CoV-2—preliminary report. N. Engl. J. Med. https://doi.org/10.1056/NEJMoa2022483 (2020). source
• Not checked yetcites [77] Feldman, R. A. et al. mRNA vaccines against H10N8 and H7N9 influenza viruses of pandemic potential are immunogenic and well tolerated in healthy adults in phase 1 randomized clinical trials. Vaccine 37, 3326–3334 (2019). source

In the paper

“encapsulation of RNA in lipid carriers 72 , and their utility in vaccination 73 , was demonstrated.”

What the sources say

• Not checked yetcites [72] Ostro, M. J., Giacomoni, D. & Dray, S. Incorporation of high molecular weight RNA into large artificial lipid vesicles. Biochem. Biophys. Res. Commun. 76, 836–842 (1977). source
• Not checked yetcites [73] Martinon, F. et al. Induction of virus-specific cytotoxic T lymphocytes in vivo by liposome-entrapped mRNA. Eur. J. Immunol. 23, 1719–1722 (1993). source

In the paper

“This group has shown that surface functionalization with InvA497 is beneficial for enhancing both in vitro cell uptake and antimicrobial efficacy of polymeric nanoparticles 69 .”

What the sources say

• Not checked yetcites [69] Castoldi, A. et al. Aspherical and spherical InvA497-functionalized nanocarriers for intracellular delivery of anti-infective agents. Pharm. Res. 36, 22 (2019). source

In the paper

“Nanoparticles can prevent, disrupt and inhibit or disperse bacteria from biofilm infections 30 (Fig. 4c).”

What the sources say

• Not checked yetcites [30] Han, C. et al. Recent developments in the use of nanoparticles for treatment of biofilms. Nanotechnol. Rev. 6, 383–404 (2017). source

In the paper

“In vitro studies revealed that antibiotics (azithromycin and rifampicin) were effective if applied immediately after infection, but not if applied after 24 or 48 h. However, encapsulation in nanoparticles partly restored their activities even when applied at 24 and 48 h after infection.”

What the sources say

• Not checked yetcites [80] Toti, U. S. et al. Targeted delivery of antibiotics to intracellular chlamydial infections using PLGA nanoparticles. Biomaterials 32, 6606–6613 (2011). source

In the paper

“nanotechnology has been most actively studied in the clinic and in large animals for the treatment and prevention of HIV infection (Table 1). In contrast, for malaria and TB, nanotechnology has been pursued with less gusto. For these IDs, work has mainly been limited to preclinical trials in rodents.”

In the paper

“Long-acting injectable nanoparticles reduce dosing frequency, which stands to improve patient adherence.”

In the paper

“These enzymes, such as β -lactamases and aminoglycoside-modifying enzymes, are readily transferred through horizontal gene transfer and have been implicated in the pattern of increasing drug resistance 3 .”

What the sources say

• Not checked yetcites [3] Munita, J. M. & Arias, C. A. Mechanisms of antibiotic resistance. Microbiol. Spectrum 4, VMBF-0016-2015. (2016). source

In the paper

“Nanoparticles have been used to protect antibiotic agents from enzymatic degradation and resensitize resistant bacteria to their bactericidal effects (Fig. 4d).”

In the paper

“Long-acting injectable antiretrovirals are the most clinically advanced nanotechnology in HIV treatment.”

In the paper

“Ten treatments at these elevated doses produced complete survival in the drug-resistant model. However, only two treatments with substantially lower doses of the liposomal combination also produced 100% survival.”

What the sources say

• Not checked yetcites [84] Schiffelers, R. M. et al. In vivo synergistic interaction of liposome-coencapsulated gentamicin and ceftazidime. J. Pharmacol. Exp. Ther. 298, 369–375 (2001).

In the paper

“In the drug-sensitive model, ten doses of the soluble drug combination treatment resulted in complete survival. Impressively, only a single dose of the liposomal combination produced the same effect.”

What the sources say

• Not checked yetcites [84] Schiffelers, R. M. et al. In vivo synergistic interaction of liposome-coencapsulated gentamicin and ceftazidime. J. Pharmacol. Exp. Ther. 298, 369–375 (2001).

In the paper

“Both nanosuspensions were safe and devoid of major adverse effects 88 .”

What the sources say

• Not checked yetcites [88] Swindells, S., Flexner, C., Fletcher, C. V. & Jacobson, J. M. The critical need for alternative antiretroviral formulations, and obstacles to their development. J. Infect. Dis. 204, 669–674 (2011). source

In the paper

“Long-chain-triglyceride-based self-microemulsifying systems containing β -artemether were demonstrated to be safe and have a notable improvement in the antimalarial activity in vivo compared with Larither.”

What the sources say

• Not checked yetcites [111] Mandawgade, S. D., Sharma, S., Pathak, S. & Patravale, V. B. Development of SMEDDS using natural lipophile: application to β-artemether delivery. Int. J. Pharm. 362, 179–183 (2008). source

In the paper

“Nanoformulation of multiple combined drugs is an efficient method for designing innovative therapeutics and can prevent resistance of the malaria parasite.”

In the paper

“Estimated half-lives of rilpivirine and cabotegravir in nanosuspensions were 44-61 days (ref. 91 ) and 25-54 days (ref. 91 ), respectively, enabling administration every 1-3 months.”

What the sources say

• Not checked yetcites [91] Verloes, R. et al. Safety, tolerability and pharmacokinetics of rilpivirine following administration of a long-acting formulation in healthy volunteers. HIV Med. 16, 477–484 (2015). source

In the paper

“Oral antiretroviral nanoparticles have been developed for paediatric use with the intent to replace tablets (which are difficult to swallow) and alcohol-containing solutions (which contain harmful excipients). These nanoparticles are produced by a novel emulsion template freeze-drying approach and have been loaded with lopinavir and efavirenz 99 .”

What the sources say

• Not checked yetcites [99] Giardiello, M. et al. Accelerated oral nanomedicine discovery from miniaturized screening to clinical production exemplified by paediatric HIV nanotherapies. Nat. Commun. 7, 13184 (2016). source

In the paper

“researchers showed that the systems resulted in greater clearance of parasites from infected mice and had a clear benefit over individual drug-loaded carriers in terms of survival period and parasitaemia progression 114 .”

What the sources say

• Not checked yetcites [114] Parashar, D., Aditya, N. P. & Murthy, R. S. R. Development of artemether and lumefantrine co-loaded nanostructured lipid carriers: physicochemical characterization and in vivo antimalarial activity. Drug Deliv. 23, 123–129 (2016). source

In the paper

“Malaria is mainly treated using chemotherapy, with artemisinin-based combination therapy being integral to curing the disease 102 .”

What the sources say

• Not checked yetcites [102] World Malaria Report 2017 (WHO, 2017); http://www.who.int/malaria/publications/world-malaria-report-2017/report/en/

In the paper

“These approaches, using oily vehicles to enhance solubilization in the gastrointestinal tract, improve drug bioavailability and patient adherence.”

In the paper

“These functionalized liposomes preferentially adhere to surface proteins decorating infected RBCs and reduce the overall parasitaemia.”

What the sources say

• Not checked yetcites [105] Marques, J. et al. Adaptation of targeted nanocarriers to changing requirements in antimalarial drug delivery. Nanomedicine13, 515–525 (2017). source
• Not checked yetcites [108] Urbán, P., Estelrich, J., Cortés, A. & Fernàndez-Busquets, X. A nanovector with complete discrimination for targeted delivery to Plasmodium falciparum-infected versus non-infected red blood cells in vitro. J. Control. Release 151, 202–211 (2011). source

In the paper

“Killing parasites in the RBCs requires prolonged treatment with high doses, which results in toxicities, potential for missed doses and development of resistance 104 .”

What the sources say

• Not checked yetcites [104] Baird, J. K. Effectiveness of antimalarial drugs. N. Engl. J. Med. 352, 1565–1577 (2005). source

In the paper

“Given that blood stage parasites are the main therapeutic target, researchers are developing various approaches to target antimalarials to infected RBCs 105-107 , thereby maximizing their therapeutic window.”

What the sources say

• Not checked yetcites [105] Marques, J. et al. Adaptation of targeted nanocarriers to changing requirements in antimalarial drug delivery. Nanomedicine13, 515–525 (2017). source
• Not checked yetcites [106] Moles, E. et al. ImmunoPEGliposomes for the targeted delivery of novel lipophilic drugs to red blood cells in a falciparum malaria murine model. Biomaterials 145, 178–191 (2017). source
• Not checked yetcites [107] Urban, P. & Fernandez-Busquets, X. Nanomedicine against malaria. Curr. Med. Chem. 21, 605–629 (2014). source

In the paper

“Nanoencapsulation enhanced circulation times of the antiretrovirals and increased their uptake into the mononuclear cells in peripheral blood and lymph nodes of macaques.”

What the sources say

• Not checked yetcites [95] Freeling, J. P., Koehn, J., Shu, C., Sun, J. & Ho, R. J. Y. Anti-HIV drug-combination nanoparticles enhance plasma drug exposure duration as well as triple-drug combination levels in cells within lymph nodes and blood in primates. AIDS Res. Hum. Retrov. 31, 107–114 (2015). source
• Not checked yetcites [96] Freeling, J. P., Koehn, J., Shu, C., Sun, J. & Ho, R. J. Y. Long-acting three-drug combination anti-HIV nanoparticles enhance drug exposure in primate plasma and cells within lymph nodes and blood. AIDS 28, 2625–2627 (2014). source

In the paper

“Although liposomal drug delivery is an established platform with proven biocompatibility, the oral route of administration is typically not used due to instability in the gastrointestinal tract 109 .”

What the sources say

• Not checked yetcites [109] Allen, T. M. & Cullis, P. R. Liposomal drug delivery systems: from concept to clinical applications. Adv. Drug Deliv. Rev. 65, 36–48 (2013). source

In the paper

“In rhesus macaques, prodrug nanoparticles maintained therapeutic concentrations of dolutegravir for ~40 days and extended the half-life of dolutegravir to ~19.5 days.”

What the sources say

• Not checked yetcites [18] Mcmillan, J. et al. Pharmacokinetics of a long-acting nanoformulated dolutegravir prodrug in rhesus macaques. Antimicrob. Agents Chemother. 62, e01316-17 (2017). source
• Not checked yetcites [94] Sillman, B. et al. Creation of a long-acting nanoformulated dolutegravir. Nat. Commun. 9, 443 (2018). source

In the paper

“NanoAbsorb is a solid microemulsion pre-concentrate formulation that can safely deliver the widely used drug artemether with higher antimalarial efficacy in vivo than the marketed formulation Larither 110 .”

What the sources say

• Not checked yetcites [110] Joshi, M., Pathak, S., Sharma, S. & Patravale, V. Solid microemulsion preconcentrate (NanOsorb) of artemether for effective treatment of malaria. Int. J. Pharm. 362, 172–178 (2008). source

In the paper

“There is only one malaria vaccine candidate that has received a positive regulatory assessment: RTS,S/AS01 (RTS,S) (Mosquirix), which is an injectable vaccine that provides partial protection against malaria in young children 115 .”

What the sources say

• Not checked yetcites [115] RTS,S Clinical Trials Partnership. A phase 3 trial of RTS,S/AS01 malaria vaccine in African infants. N. Engl. J. Med. 367, 2284–2295 (2012). source

In the paper

“Therefore, researchers are attempting to improve the existing BCG vaccine and derive new vaccines to prevent TB 133 .”

What the sources say

• Not checked yetcites [133] Kaufmann, S. H. E., Weiner, J. & von Reyn, C. F. Novel approaches to tuberculosis vaccine development. Int. J. Infect. Dis. 56, 263–267 (2017). source

In the paper

“In July 2015, European regulators approved the use of the vaccine, although it is at most 50% effective 115 .”

What the sources say

• Not checked yetcites [115] RTS,S Clinical Trials Partnership. A phase 3 trial of RTS,S/AS01 malaria vaccine in African infants. N. Engl. J. Med. 367, 2284–2295 (2012). source

In the paper

“Researchers have developed nebulized solid lipid particles 129 and sodium alginate nanoparticles 130 incorporating rifampicin, isoniazid and pyrazinamide to improve targeted bioavailability in the lungs and reduce hepatotoxicity.”

What the sources say

• Not checked yetcites [129] Pandey, R. & Khuller, G. K. Solid lipid particle-based inhalable sustained drug delivery system against experimental tuberculosis. Tuberculosis 85, 227–234 (2005). source
• Not checked yetcites [130] Zahoor, A., Sharma, S. & Khuller, G. K. Inhalable alginate nanoparticles as antitubercular drug carriers against experimental tuberculosis. Int. J. Antimicrob. Agents 26, 298–303 (2005). source

In the paper

“Bacillus Calmette-Guerin (BCG), which was introduced in 1921, is the sole approved TB vaccine, but it offers only limited protection 132 .”

What the sources say

• Not checked yetcites [132] Hawn, T. R. et al. Tuberculosis vaccines and prevention of infection. Microbiol. Mol. Biol. Rev. 78, 650–671 (2014). source

In the paper

“The antigen is formulated as virus-like particle and combined with a liposomal adjuvant system.”

What the sources say

• Not checked yetcites [115] RTS,S Clinical Trials Partnership. A phase 3 trial of RTS,S/AS01 malaria vaccine in African infants. N. Engl. J. Med. 367, 2284–2295 (2012). source

In the paper

“Unless radical action is taken, drug-resistant strains of M. tuberculosis will account for 25% of antimicrobial resistance-related deaths and cost the global economy US$16.7 trillion by the year 2050 119 .”

What the sources say

• Not checked yetcites [119] O’Neill, J. Tackling Drug-Resistant Infections Globally: Final Report and Recommendations (2016).

In the paper

“Given that most people with TB infection do not have symptoms, it can be challenging for them to complete their regimens 139 .”

What the sources say

• Not checked yetcites [139] Van Ginderdeuren, E., Bassett, J., Hanrahan, C., Mutunga, L. & Van Rie, A. Health system barriers to implementation of TB preventive strategies in South African primary care facilities. PLoS ONE 14, e0212035 (2019). source

In the paper

“Innovative and cost-effective nanotechnologies that take into consideration the challenges that are encountered low SDI countries are most likely to benefit patients.”

In the paper

“In 2006, the International Centre for Technology Assessment and other consumer groups filed a legal petition against the FDA for perceived lack of initiative in regulating nanomaterial-containing products under their jurisdiction.”

What the sources say

• Not checked yetcites [145] Nanotechnology: A Report of the US Food and Drug Administration Nanotechnology Task Force (USFDA, 2007).

In the paper

“TB is caused by the inhalation of droplet nuclei containing M. tuberculosis that enter the respiratory tract and infect the alveoli of the lungs.”

What the sources say

• Not checked yetcites [149] Pai, M. et al. Tuberculosis. Nat. Rev. Dis. Prim. 2, 16076 (2016). source

In the paper

“It is also recommended that people who are infected with TB but do not have active disease (latent TB) receive treatment to eradicate the mycobacteria and prevent progress to active disease 138 .”

What the sources say

• Not checked yetcites [138] Latent Tuberculosis Infection: Updated and Consolidated Guidelines for Programmtic Management (WHO, 2018).

In the paper

“Nonetheless, the rapid translation of nanotechnologies from the bench to the people, and the impact that these systems have had on the SARS-CoV-2 pandemic provide great promise.”

In the paper

“The examples above highlight many promising therapeutic strategies for developing nanomedicines to treat and prevent IDs.”

In the paper

“Nanotechnology is a multi-disciplinary field that also requires intellectual property and commercialization strategies to grow 146 .”

What the sources say

• Not checked yetcites [146] Bhatia, P., Vasaikar, S. & Wali, A. A landscape of nanomedicine innovations in India. Nanotechnol. Rev. 7, 131–148 (2018). source

In the paper

“However, to have the maximum impact, nanotechnology solutions will need to overcome several financial, manufacturing and regulatory challenges.”

In the paper

“Simplifying the use of medicines and making drugs safer and more efficacious can improve patients' quality of life and reduce disease burden.”

In the paper

“The FDA created a Nano Task Force in response 145 .”

What the sources say

• Not checked yetcites [145] Nanotechnology: A Report of the US Food and Drug Administration Nanotechnology Task Force (USFDA, 2007).

In the paper

“Nanotechnology can potentially simplify dosing and minimize adverse events in this population, thereby greatly contributing to the elimination of TB.”

In the paper

“This example suggests that similar feats may be possible in treating other infectious diseases as well.”